Nephron
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Glomerular hyperfiltration (GH) is a hallmark of renal dysfunction in diabetes and obesity. Recent clinical trials demonstrated that SGLT2 inhibitors are renoprotective, possibly by abating hyperfiltration. The present review considers the current evidence for a cause-to-effect relationship between hyperfiltration-related physical forces and the development of chronic kidney disease (CKD). ⋯ Glomerular hyperfiltration is associated with glomerular and tubular hypertrophy. Hyperfiltration is mainly due to an increase in glomerular capillary pressure, which increases tensile stress applied to the capillary wall structures. In addition, the increased ultrafiltrate flow into Bowman's space heightens shear stress on the podocyte foot processes and body surface. These mechanical stresses lead to an increase in glomerular basement membrane (GBM) length and to podocyte hypertrophy. The ability of the podocyte to grow being limited, a mismatch develops between the GBM area and the GBM area covered by foot processes, leading to podocyte injury, detachment of viable podocytes, adherence of capillaries to parietal epithelium, synechia formation and segmental sclerosis. Mechanical stress is also applied to post-filtration structures, resulting in dilation of glomerular and tubular urinary spaces, increased proximal tubular sodium reabsorption by hypertrophied epithelial cells and activation of mediators leading to tubulointerstitial inflammation, hypoxia and fibrosis Key Messages: GH-related mechanical stress leads to both adaptive and maladaptive glomerular and tubular changes. These flow-related effects play a central role in the pathogenesis of glomerular disease. Attenuation of hyperfiltration is thus an important therapeutic target in diabetes and obesity-induced CKD.
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Although the epidemiology of acute kidney injury (AKI) has been well described, less is known about recurrent AKI (r-AKI). We undertook a systematic review to identify incidence, risk factors, and outcomes of r-AKI. ⋯ From 2,824 citations, 10 cohort studies met inclusion criteria (total patients n = 538,667). There were 2 distinct set of studies; 4 studies assessed r-AKI within the same hospital admission (most were intensive care unit [ICU] patients) and 6 studies assessed postdischarge r-AKI. The median percentage of people developing r-AKI within the same hospital admission was 23.4% (IQR 20.3-27.2%) and postdischarge r-AKI was 31.3% (IQR 26.4-33.7%). A higher Acute Physiology and Chronic Health Evaluation score was associated with increased risk of r-AKI within the same hospital admission in ICU patients. Cardiovascular disease and AKI severity were associated with increased risk of postdischarge r-AKI. R-AKI (within same admission and postdischarge) was associated with worse survival. It was not possible to pool results due to methodological differences across studies, such as varying definitions for AKI and r-AKI, varying length of follow-up and effect measures. Key messages: More representative population-based studies with robust assessment of predictors and consensus definition of r-AKI are needed to identify risk factors and develop risk stratification tools to reduce recurrence and improve outcomes. Systematic Review Registration: CRD42017082668.